JP2013203736A - Tablet - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a tablet containing a component having inferior shape retention but having sufficient hardness as a tablet, and suppressed in generation of capping.SOLUTION: There is provided a tablet containing a component having inferior shape retention and cellulose, wherein the average L/D value of the cellulose is ≥3.

Description

  The present invention relates to a tablet. More specifically, the present invention relates to a tablet containing an ingredient having poor shape retention.

  Examples of pharmaceutical and health food dosage forms include powders, granules, capsules and tablets. Among these, tablets are a widely used dosage form because they are easy to handle and take.

  However, for example, when tablets are produced by compressing a material with poor shape retention such as glucosamine, there is a problem that the desired hardness cannot be obtained and the tablet breaks. This causes a problem that a phenomenon called “occurs” occurs and causes a product defect. Therefore, as a method for solving such product defects, the content of binders, excipients, etc. to be blended into the tablet is added for the purpose of supplementing the shape retention of the tablet and making the tablet have an appropriate hardness. There are known ways to increase it. However, if the content of binders, excipients, etc. in the tablet is increased in such a way, the content of the active ingredient in the tablet decreases, so in order to obtain the effect of the active ingredient sufficiently, many tablets are taken. The problem of having to do arises.

  As a method for solving such problems, conventionally, a method of granulating a mixture of glucosamine and / or a salt thereof and N-acetylglucosamine and then tableting (Patent Document 1), glucosamine and / or a salt thereof, A method of tableting after spraying a solution containing other saccharides or granulating while spraying (Patent Document 2), for granulation refined into a powder having poor compression moldability such as glucosamine A method of producing tablets with sufficient hardness while containing many active ingredients with poor shape retention, such as a method of tableting a granulated product after uniformly attaching a binder (Patent Document 3) Proposed. However, Patent Document 1 uses expensive N-acetylglucosamine, which increases the manufacturing cost of tablets. In Patent Documents 2 and 3, granulation is performed by spraying an aqueous solution separately prepared on glucosamine powder. However, there is a problem that the manufacturing process becomes complicated.

JP 2007-238486 A JP 2006-36644 A JP 2010-285381 A

  An object of the present invention is to provide a tablet that contains a component having poor shape retention but has sufficient hardness as a tablet and suppresses the occurrence of capping. More preferably, an object of the present invention is to provide a tablet having excellent formulation characteristics while containing at least 80% by mass of a component having poor shape retention.

  As a result of studies to solve the above problems, the inventor of the present invention contains tablets having an average L / D value of a certain level or more together with a component having poor shape retention, and thus tablets having excellent formulation characteristics for the above purpose. Was found and the present invention was completed. That is, the present invention has the following embodiments.

  Item 1. A tablet containing a component having poor shape retention and cellulose, wherein the cellulose has an average L / D value of 3 or more.

  Item 2. Item 2. The tablet according to Item 1, wherein the component having poor shape retention is at least one selected from the group consisting of glucosamine or a salt thereof, ascorbic acid or a salt thereof, and a dried pulverized product of a plant.

  Item 3. Item 3. The tablet according to Item 1 or 2, comprising the component having poor shape retention at a ratio of 80% by mass or more.

  Item 4. The component having poor shape retention is (a) a component having poor compression moldability, (b) a component having a water content of 1% by mass or less, (c) a crystalline component, and (d) a bulk density of 0.8 g. Item 2. The tablet according to Item 1, wherein the tablet is at least one selected from the group consisting of components of at least / ml.

  Item 5. Item 2. The tablet according to Item 1, wherein the tablet has a hardness of 1.5 kgf or more.

  According to the present invention, as cellulose to be blended together with a component having poor shape retention, a tablet having an average L / D value of 3 or more has sufficient hardness as a tablet and generation of capping is suppressed. Can be provided. For this reason, according to this invention, generation | occurrence | production of the product defect of a tablet can be suppressed.

  In addition, according to the present invention, by blending the specific cellulose in the tablet, it becomes possible to form a component having poor shape retention as a tablet having sufficient hardness. Additives such as other required binders are not blended, or the blending amount can be reduced. For this reason, a tablet containing a high content of ingredients having poor shape retention can be prepared.

  Therefore, if the active ingredient is an ingredient with poor shape retention, the content of the active ingredient in the tablet can be increased, so the size of the dosage form per tablet can be reduced or taken once The number of per tablet can be reduced, and as a result, the burden on the person who takes the tablet can be reduced.

  Hereinafter, the tablet of this invention and its manufacturing method are demonstrated.

(1) Tablet The tablet of the present invention contains a component having poor shape retention and cellulose, and the average L / D value of the cellulose is 3 or more.

(1-1) Ingredients with poor shape retention As described above, the tablet of the present invention contains ingredients with poor shape retention.

  Ingredients with poor shape retention targeted by the present invention include at least (a) a component inferior in compression moldability, (b) a component having a water content of 1% by mass or less, (c) a crystalline component, and (d ) A component having a bulk density of 0.8 g / ml or more is included.

  Hereinafter, although these components are demonstrated, when it corresponds to at least one of these components, it can be called "a component with poor shape retention" which this invention makes object.

(A) Component compression moldability that is inferior to compression moldability refers to the property that powder particles bind to each other when pressure is applied to the powder, and it is possible to compress an amorphous powder into a specific shape Refers to special characteristics.

  Ingredients that are inferior in compression moldability are inherently small in the nature that the ingredients themselves bind to each other, and in order to form tablets with appropriate hardness, a binder or the like must be present at a relatively high rate, As a result, it is difficult to improve the content of the component itself in the tablet. Specifically, for example, as shown in an experimental example to be described later, when cellulose having an average L / D value of 2.8 or less is used as a binder, the content in the tablet is increased by more than 80% by mass. The component which cannot be made corresponds to a thing inferior to compression moldability.

  Moreover, as a component inferior to compression moldability, the component whose compression degree is 20% or less, Preferably it is 15% or less, More preferably, it is 10% or less can be mentioned. Here, the degree of compression is a fluidity index representing the fluidity and tabletability of the powder, and can be determined by the following method.

(How to determine the degree of compression)
The degree of compression (%) of the component having inferior compression moldability of the present invention is represented by the following formula.

Compressibility (%) = [(ρP−ρA) / ρP] × 100
(However, ρA = bulk density in a loosely packed state (g / cm ³ ), ρP = bulk density when tightly packed after tapping (g / cm ³ ))
The definition of the degree of compression, the measurement conditions, and the like are the methods described in Nikkei Technical Books Co., Ltd., edited by the Powder Engineering Society, “Revised Supplement, Issued by Physical Properties of Powder, December 1985, pages 151-152.

For example, a component having poor compression moldability can be measured with a powder tester (manufactured by Hosokawa Micron Corporation). As a specific measurement method, it is supplied uniformly from above through a 24-mesh sieve to a cylindrical container with a diameter of 5.03 cm and a height of 5.03 cm (volume: 100 g / cm ³ ), and the upper surface is ground and weighed. The bulk density (ρA, apparent bulk density) is measured. Next, a cylindrical cap is put on the container, powder is added to the upper edge, and tapping with a tap height of 1.8 cm is performed 180 times. After completion, the cap is removed, the powder is ground on the upper surface of the container and weighed, and the bulk density (ρP, tapping density) when tightly packed after tapping is measured. The degree of compression (%) can be obtained by substituting the obtained numerical value into the above equation.

  Examples of components inferior in compression moldability include, for example, glucosamine or a salt thereof, calcium, chitosan, chitin, chondroitin sulfate, N-acetylglucosamine, MSM, western willow, amino acids (arginine, taurine, glutamic acid, histidine, branched chain amino acids (leucine, Isoleucine, valine)), citric acid, acetic acid, chitin dimer, chitin pentamer, chitosan hexamer, oligoglucosamine, pepper, ginseng, beer yeast, baker's yeast, yeast zinc, yeast selenium and the like.

  Here, glucosamine is 2-aminoglucose in which the hydroxyl group at the 2-position of glucose is substituted with an amino group, and is widely distributed in important biological components such as glycoproteins, glycolipids and mucopolysaccharides which are biological components. Natural amino sugar. The glucosamine salt is not particularly limited as long as it is a pharmaceutically acceptable salt, but is a salt with an inorganic acid such as hydrochloric acid, sulfuric acid, nitric acid or phosphoric acid; citric acid, succinic acid Salts with organic acids such as acid, acetic acid, tartaric acid or lactic acid can be exemplified. Preferred are glucosamine inorganic acid salts such as glucosamine hydrochloride and glucosamine sulfate.

  Glucosamine or a salt thereof is known to have a joint pain relieving effect, a blood flow promoting effect, and a skin beautifying effect. For this reason, glucosamine or a salt thereof is useful as an active ingredient of a supplement (food product), a quasi-drug or a pharmaceutical product having the above-mentioned function.

(B) Component having a water content of 1% by mass or less A component having a water content of 1% by mass or less does not exhibit sufficient gelling power, adhesive strength, etc., and generally has poor shape retention.

  The water content in the components can be measured by the following method.

(Method for measuring moisture content)
First, the target sample component is left at a temperature of 25 ° C. and a relative humidity of 40% for the number of days (one day) at which the moisture in the component reaches equilibrium. Next, after measuring the weight (wet weight) of each 1 g of the obtained sample, the sample was heated at 105 ° C. for 4 hours under normal pressure conditions in accordance with the general test method “loss on drying test method” prescribed in the 16th revised Japanese Pharmacopoeia. Process and measure weight (dry weight) again. By subtracting the dry weight from the wet weight obtained in such a test method, the loss on drying (%) is calculated by the following equation.

Loss on drying (%) =
[(Wet weight of sample component−dry weight of sample component) / wet weight of sample component] × 100

  The weight loss (%) thus obtained can be defined as the moisture content of the sample components (1 g, 105 ° C., 4 hours). According to this test method, for example, when a weight of about 1 g of a sample component left at a temperature of 25 ° C. and a relative humidity of 40% for 1 day is accurately weighed and dried at 105 ° C. for 4 hours, the weight loss is 10 mg per gram of the component. When it is below, it can be judged that the water content is 1% by mass or less.

  Examples of the component having a water content of 1% by mass or less include, in addition to the above-mentioned glucosamine or a salt thereof, dry pulverized products of plants, dolomite, and the like.

  Here, examples of the dry pulverized product of the plant include a product obtained by pulverizing a dried product of the plant into an appropriate size and pulverizing it, or a product obtained by drying the pulverized product of the plant according to a standard method. Here, the drying method is not particularly limited, and spray drying, vacuum drying, freeze drying and the like can be used. In addition, the dried and pulverized product of the plant of the present invention includes a product obtained by pulverizing a plant juice or extract by a drying process such as spray drying, vacuum drying or freeze drying.

(C) Crystalline component The crystalline component generally has poor shape retention because of its poor plastic deformability. Among the crystalline components, components having a needle-like crystal structure, a prismatic crystal structure, or a plate-like crystal structure are particularly poor in shape retention.

  Whether or not the object is a crystalline component can usually be determined by microscopic observation with a scanning electron microscope or the like.

  As a crystalline component, ascorbic acid or its salt, an amino acid etc. are mentioned, for example. In particular, ascorbic acid or a salt thereof has an acicular crystal structure.

  Here, ascorbic acid may be any of D-ascorbic acid, L-ascorbic acid, and DL-ascorbic acid, but is preferably L-ascorbic acid. The salt of ascorbic acid is not particularly limited as long as it is a pharmaceutically acceptable salt of ascorbic acid, and specific examples include alkali metal salts such as sodium ascorbate. Can do.

(D) The component bulk density having a bulk density of 0.8 g / ml or more means the mass of the sample component per unit bulk volume. More specifically, as defined in the 16th revision Japanese Pharmacopoeia, the ratio of the mass of the sample component in a non-tapped (loosened) state to the volume of the sample component including the interparticle void volume factor. .

  The bulk density can be determined by filling a sample component in a container having a known volume and measuring the mass thereof. Specifically, it can be measured and determined using the first method (method using a graduated cylinder) of the general test method “bulk density measurement method” defined in the 16th revised Japanese Pharmacopoeia.

  In the present invention, a component having a bulk density in the range of 0.8 g / ml or more can be said to be a component having poor shape retention. When the bulk density of the component exceeds 0.8 g / ml, the gap between particles becomes large when forming into a tablet, and it is difficult to sufficiently improve the content of the component with poor shape retention incorporated into the tablet. Tend to be.

  As described above, (a) a component inferior in compression moldability, (b) a component having a water content of 1% by mass or less, (c) a crystalline component, (d) a bulk density of 0.8 g / ml or more If it corresponds to at least one of the components which are, it will correspond to the component with bad shape-retaining property said by this invention. As described above, as described above, glucosamine or a salt thereof, ascorbic acid or a salt thereof, a dry pulverized product of a plant, dolomite, calcium, chitosan, chitin, chondroitin sulfate, N-acetylglucosamine, MSM, a willow, Amino acids (arginine, taurine, glutamic acid, histidine, branched chain amino acids (leucine, isoleucine, valine)), citric acid, acetic acid, chitin dimer, chitin pentamer, chitosan hexamer, oligoglucosamine, red pepper, ginseng, beer yeast, bread Examples thereof include yeast, yeast zinc, yeast selenium and the like.

  The tablet of the present invention may contain one of these poorly shape-retaining components, or may contain any combination of two or more poorly shape-retaining components. Good.

Average particle size of components with poor shape retention The components with poor shape retention targeted by the present invention fall under any shape as long as they fall under at least one of the above-exemplified components, and are powdery or pulverized Or it may have a granular shape.

  The size (particle size) is not particularly limited, but the average particle size is preferably 1 to 2000 μm. Preferably it is 5 to 1500 micrometers, More preferably, it is 10 to 1000 micrometers.

  Here, the average particle diameter means the particle diameter at an integrated value of 50% in the particle size distribution obtained by the laser diffraction / scattering method. The laser diffraction / scattering method is a method for measuring the particle size by utilizing the difference in the light intensity distribution of the diffracted and scattered light depending on the particle size when laser light is applied to the particle. The particle size distribution measuring device (for example, “Laser particle size analyzer SALD-2200” manufactured by Shimadzu Corporation) can be used.

Content ratio of component having poor shape retention It is preferable that the component having poor shape retention is filled as densely as possible into the molded tablet.

  The content ratio of the poorly shape-retaining component in the tablet of the present invention is not particularly limited, but when it is an active ingredient of a tablet, it is preferably 70% by mass or more, more preferably 80% by mass or more. More preferably, it is 85 mass% or more, More preferably, it is 90 mass% or more, Most preferably, it is 95 mass% or more.

  The active ingredient is a substance that exhibits a physiological action or pharmacological activity intended in the body after being administered or ingested to the human body, and is also referred to as a functional substance in that sense.

(1-2) Cellulose having an average L / D value of 3 or more The cellulose used in the tablet of the present invention has an average L / D value of 3 or more. This cellulose functions as a binder for the above-mentioned components having poor shape retention in the tablet of the present invention.

  The form of the cellulose is not particularly limited as long as it satisfies the above average L / D value. Examples of the form include powder, particles, and crystals.

  The average L / D value of cellulose is the ratio of the major axis (L) (major axis length) to the minor axis (D) (minor axis length) of cellulose having a powdery, particulate or crystalline form. The major axis (L) and the minor axis (D) can be determined by microscopic observation using a scanning electron microscope (for example, S-800A type manufactured by Hitachi, Ltd.).

  Specifically, first, the target cellulose (particulate, powdery, etc.) is placed on a speculum sample stage, and a metal such as gold or platinum is vapor-deposited by an ion sputtering apparatus or the like to obtain a speculum sample. . Next, the microscopic sample is observed at an accelerating voltage of 5 KV, for example, with an enlargement magnification of 3000 times, and the major axis (L) and minor axis (D) of 50 randomly extracted particles are measured from the obtained image. / D value is calculated and the average value is adopted. Alternatively, the major axis (L) and minor axis (D) of 50 randomly extracted particles are measured, and the average L / D value is calculated from the average value (average major axis (L), average minor axis (D)). calculate.

  The cellulose used in the tablet of the present invention may have an average L / D value of 3 or more, and the upper limit is not particularly limited, but the upper limit is preferably about 5. The average L / D value of cellulose is preferably 3 to 4, more preferably 3 to 3.5. In addition, the cellulose used in the tablet of the present invention may have an average L / D value of 3 or more, and as long as the size (particle diameter) is not particularly limited, About 10-250 micrometers, Preferably it is about 25-200 micrometers, More preferably, about 40-100 micrometers can be mentioned. The definition of the average particle diameter and the measuring method are as described above.

  Although the content rate of the cellulose in the tablet of the present invention is not limited, it can usually be 30% by mass or less in relation to the content rate of the component having poor shape retention described above. Preferably it is 20 mass% or less, More preferably, it is 15 mass% or less, More preferably, it is 10 mass% or less, Most preferably, it is 5 mass% or less. The lower limit of the cellulose content contained in the tablet of the present invention is preferably about 4% by mass.

  Moreover, although the said cellulose is not restrict | limited with respect to 100 mass parts of components with bad shape retention contained in the tablet of this invention, It is preferable to mix | blend in the ratio of about 4-25 mass parts. A more preferable ratio is about 5 to 15 parts by mass, and a particularly preferable ratio is about 6 to 10 parts by mass.

Other components The tablet of the present invention may contain components other than the above components (components with poor shape retention, cellulose having an average L / D of 3 or more), as long as the effects of the present invention are not impaired. it can. Examples of such other components include functional substances other than the aforementioned poorly shape-retaining components, and pharmaceutically acceptable carriers or additives used in the production of tablets.

  Here, as the functional substance, for example, hyaluronic acid, ceramide, collagen, red ginger extract, various polyphenols (from apple, tea, guava, pine, grape, etc.) can be used in combination. Other examples include octacosanol, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid, and the like.

  Examples of pharmaceutically acceptable carriers or additives include, for example, excipients, binders, disintegrants, lubricants, flavoring agents, coloring agents, sweeteners, corrigents, solubilizers, suspensions. Agents, emulsifiers, coating agents, antioxidants and the like can be included. Various components corresponding to these carriers or additives are known, and can be arbitrarily selected and used. For example, examples of the lubricant include talc, purified talc, magnesium stearate, hydrogenated vegetable oil, polyglycerol fatty acid ester, and sucrose fatty acid ester. Preferably it is magnesium stearate.

  As described above, the content of the above other components in the tablet hinders the effects of the present invention (containing many components having poor shape retention, sufficient hardness, suppression of capping, etc.). It may be within a range, and is usually about 30% by mass or less, preferably about 20% by mass or less, more preferably about 10% by mass or less.

Hardness, shape and size of tablet The tablet of the present invention is characterized in that it has sufficient hardness as a tablet despite the high content of the above-mentioned components having poor shape retention.

  The hardness of the tablet of the present invention is preferably about 1.5 kgf or more, although it depends on the type of ingredients having poor shape retention. More preferably, it is about 5-15 kgf, More preferably, it is about 8-12 kgf.

  Specifically, when, for example, glucosamine or a salt thereof is used as a component having poor shape retention, the hardness of a tablet containing it is preferably about 2 kgf or more. More preferably, it is about 5-15 kgf, More preferably, it is about 8-12 kgf. When, for example, ascorbic acid or a salt thereof is used as a component having poor shape retention, the hardness of the tablet containing it is preferably about 1.5 kgf or more. More preferably, it is about 3-10 kgf, More preferably, it is about 6-8.5 kgf.

  If the tablet hardness is within the above range, the dosage form of the tablet does not collapse during production, transportation, and ingestion, etc., and it has sufficient dosage form maintainability and can be used for PTP packaging. The hardness of the tablet can be determined by measuring the hardness of a plurality of (for example, 10) tablets using a load cell type hardness tester and obtaining an average value thereof.

  The tablet of the present invention is not particularly limited with respect to its shape, size and the like. Examples of the shape include all shapes such as a round shape, an elliptical shape, a triangular shape, and a square shape. About a magnitude | size, it can be set as the dosage form of diameter 5mm-20mm, Preferably 7-10mm; weight 100mg-2000mg.

  In addition, the tablet of the present invention may be an uncoated tablet (bare tablet), or a coated tablet whose surface is coated for the purpose of stabilizing the drug and taste-masking or flavoring. Coated tablets include sugar-coated tablets and film coating agents (gastric tablets, enteric tablets) coated with a film containing a water-soluble, enteric or gastric polymer base.

  Furthermore, the use of the tablet of the present invention is not limited, and it may be a pharmaceutical, a quasi-drug, or a food. Further, the usage is not limited, and it may be a tablet for internal use, an oral tablet (troche tablet, buccal tablet, sublingual tablet, chewable tablet, orally disintegrating tablet), or external tablet.

(2) Manufacturing method of tablet The tablet of this invention can be manufactured by the direct tableting method or the granule tableting method according to the conventional method of this industry. A granulation tableting method is preferred in which the mixed raw materials are once granulated and then tableted.

  When manufacturing a tablet by the direct tableting method, it is not limited, but first, an ingredient having poor shape retention and cellulose (average L / D value is 3 or more) are provided in a mortar of a rotary disk of a tableting machine. It can be manufactured by compressing with upper and lower eyelids. In the mixture, the above-mentioned “other components” such as a functional substance, or a pharmaceutically acceptable carrier or additive (a binder other than the cellulose, an excipient, a disintegrant, a lubricant, etc.) is added. You may mix | blend as an arbitrary component.

  When tablets are produced by the granule tableting method, there is no limitation, but first, water and / or an organic solvent is added to a mixed powder of a component having poor shape retention and cellulose (average L / D value is 3 or more). In addition, after granulating once and adjusting the size as necessary, the prepared granule is subjected to a tableting machine and compressed (tablet) with an upper punch and a lower punch. In the mixed powder, the above-mentioned “other components”, for example, functional substances, or pharmaceutically acceptable carriers or additives (such as binders other than cellulose, excipients, and disintegrants) are arbitrarily added. It may be blended as an ingredient, and after sizing and before tableting, a pharmaceutically acceptable carrier or additive (a binder other than cellulose, an excipient, a disintegrant, etc.) may be blended as an optional ingredient. Also good.

  The granulation is usually performed using a conventional granulator. Examples of such a granulator include a fluidized bed granulator, a stirring granulator, and an extrusion granulator. The granulation is not particularly limited. For example, in the granulation tank of the granulator, the component having poor shape retention and cellulose are mixed, and the mixture is uniformly sprayed with a binder such as water or ethanol. Can be done. Under the present circumstances, conditions at the time of granulation, such as the intake air temperature in a granulation tank, the temperature of a spray liquid, can be set suitably, but 40-90 degreeC is preferable normally, and intake temperature is more preferable 40-70 degreeC. Moreover, 10-80 degreeC is preferable and the temperature of a spray liquid has more preferable 20-60 degreeC.

  The granulated product (granules) thus obtained is dried as necessary to remove the contained water and organic solvent. Here, the drying temperature is preferably 20 to 90 ° C. More preferably, it is 30-85 degreeC, and 65-80 degreeC is still more preferable. Thus, the granules are dried so that the moisture content is preferably 3% by mass or less, more preferably 2% by mass or less.

  The dried granules can be appropriately sized as necessary, for example, 18 to 22 mesh, preferably 12 to 20 mesh.

  The granules are then compressed into tablets. Tableting is performed, for example, by filling the granule into a cylindrical mortar, grinding the filled granule to a certain amount with a grinding plate, and compressing it with upper and lower scissors. As the tableting machine, a known apparatus such as a high-speed rotary tableting machine can be used without limitation.

The operating conditions such as tableting pressure vary depending on the shape and size of the tablet to be produced, and are not particularly limited. For example, a tableting machine equipped with a punch having a diameter of 5 to 20 mm and a curvature radius of 6 to 24 mm is used. Used, the granule of the mixture containing the above-mentioned component having poor shape retention and cellulose is tableted. For example, when producing a round tablet of 100 to 2000 mg / tablet, it is preferable to tablet form under a tableting pressure of 600 to 2500 kgf / cm ² .

  The tablet produced in this way can hold a tablet hardness of about 1.5 to 15 kgf while containing the above-mentioned components with poor shape retention. A more preferable tablet of the present invention is capable of holding a tablet hardness of about 1.5 to 15 kgf while containing 70% by mass or more, preferably 80% by mass or more of the above-mentioned component having poor shape retention.

  Hereinafter, although an example and a comparative example explain the present invention still in detail, the present invention is not limited by these examples.

Experimental example
(1) Tablet component Glucosamine: Glucosamine GM-C manufactured by Protein Chemical Co., Ltd., average particle size 100 μm, bulk density 0.3 g / ml
VC (ascorbic acid): fine powder of ascorbic acid manufactured by DSM Nutrition Japan Co., Ltd., average particle size 80 μm, bulk density 0.7 g / ml
Cellulose A: Cellulose ST-100 manufactured by Asahi Kasei Chemicals Corporation, average L / D value 3.5, average particle size 50 μm
Cellulose B: Cellulose ST-02 manufactured by Asahi Kasei Chemicals Corporation, average L / D value of 2.8, average particle diameter of 50 μm
Calcium stearate: lubricant, Aubrite CA-65 manufactured by NOF Corporation, average particle size 8μm
Average L / D value of cellulose (ratio of major axis (L) to minor axis (D))
From the mixing ratio of cellulose A (ST-100, average L / D value 3.5) and cellulose B (ST-02, average L / D value 2.8), the average L / D value of cellulose contained in the tablet Was calculated.

(2) Preparation of tablets Table 1 shows the compositions of tablets containing glucosamine as an active ingredient (Examples A1 to A12 and Comparative Examples a1 to a3), and Table 2 shows tablets containing ascorbic acid as an active ingredient (Example B1). -B12 and the composition of Comparative Examples b1-b3) are described. The tablets were produced according to the granule tableting method.

Preparation of granules Glucosamine powder or ascorbic acid was mixed to prepare granules (granulated product). For granulation, agitation granulator (VG-300, manufactured by Paulec Co., Ltd., charged amount: 200 kg of powder) was used, and granulation was performed under the conditions of chopper: 3600 rpm, blade: 140 rpm, temperature: 25 ° C. . About glucosamine, it granulated with the water content of 3.0 mass%. For VC (ascorbic acid), only mixing was performed.

  The obtained granulated powder was sized with a comil (manufactured by Paulec Co., Ltd., 1.0φ screen, 30 Hz).

  It mixed with the container mixer (20 rpm).

Tablet preparation powder is obtained by mixing cellulose (ST-100, ST-02) and calcium stearate (St-Ca) as a lubricant so that the blended amount shown in Tables 1 and 2 can be obtained. It was. Using a tableting machine ("HT-AP12SS-U" manufactured by Hata Iron Works), a pressure of 2.0t was applied with a hydraulic press, and the tableting powder was compressed with a special mold (manufactured by Kikusui Seisakusho). Processing was performed to obtain tablets of 8 mm round φ250 mg.

(3) Tablet evaluation test
Measurement of tablet hardness Using a load cell type tablet hardness tester (Okada Seiko Co., Ltd., portable checker PC-30 type), the hardness of the obtained tablet was hit under the conditions of room temperature 25 ° C. and humidity 40%. Measured immediately after locking (n = 3). The results are shown in Tables 1 and 2 together.

Measurement of tablet capping rate Using a friability tester (TFT-1200, manufactured by Toyama Sangyo Co., Ltd.), obtained immediately after tableting under conditions of room temperature 25 ° C, humidity 40%, 45 rpm, 3 minutes. The incidence of capping of the tablets was measured. From the capping occurrence rate, the acceptability as a tablet product was evaluated according to the following criteria. The results are shown in Tables 1 and 2 together.

A: Capping does not occur (occurrence rate 0%).
○: The occurrence rate of capping is less than 35%, which is acceptable as a tablet product.
(Triangle | delta): The incidence rate of capping is 35% or more and less than 65%, and is unsatisfactory as a tablet product.
X: The occurrence rate of capping is 65% or more, which is poor as a tablet product.

Comprehensive evaluation The prepared tablets (Examples A1 to A12 and B1 to B12, Comparative examples a1 to a3 and b1 to b3) were comprehensively evaluated according to the following criteria. The results are shown in Tables 1 and 2 together.

A: The hardness is 8 kgf or more, and the capping occurrence rate is evaluated as ◎.
B: Hardness is less than 5-8 kgf, and capping occurrence rate is evaluated as ◎ or ◯.
C: Hardness is less than 1.5 to 5 kgf, and capping occurrence rate is evaluated as ◎ or ◯.
D: The hardness is less than 1.5 kgf, or the capping occurrence rate is evaluated as Δ or ×.

  Examples using glucosamine as a component with poor shape retention are shown in Table 1, and examples using ascorbic acid as a component with poor shape retention are shown in Table 2.

<Discussion>
As shown in Tables 1 and 2, from the test results, cellulose having an average L / D value of 3 or more is used even when it contains 80% by mass or more of components having poor shape retention properties such as glucosamine and ascorbic acid. As a result, it was possible to produce a tablet having a hardness that is preferable as a tablet having a hardness of 1.5 kgf or more and with reduced occurrence of capping, without adding any other carrier or additive such as a binder. (Examples A1-12 and Examples B1-12). On the other hand, as shown in Comparative Examples a1 to a3 and b1 to b3, the cellulose having an average L / D value of 2.8 or less could not produce a tablet having the above characteristics. .

Claims (3)

A tablet containing a component having poor shape retention and cellulose, wherein the cellulose has an average L / D value of 3 or more. The tablet according to claim 1, wherein the component having poor shape retention is at least one selected from the group consisting of glucosamine or a salt thereof, ascorbic acid or a salt thereof, and a dried pulverized product of a plant. The tablet according to claim 1 or 2, comprising the poorly shape-retaining component in a proportion of 80% by mass or more.